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Research Group Kolahian

The main focus of research in our lab is to investigate the emerging therapeutic role of regulatory immune cells particularly myeloid derived suppressor cells (MDSCs) in lung diseases such as asthma, asthma tolerance / exacerbation and pulmonary fibrosis.

Background: Myeloid derived suppressor cells (MDSCs)

Suppressive myeloid cells were initially identified more than three decades ago in patients with cancer. Later on, these cells were uniformly termed as myeloid-derived suppressor cells (MDSCs). MDSCs are not defined as a single subset of cells, but rather represent a group of phenotypically heterogeneous myeloid cells that share a common biological activity i.e. suppressing T cells. Despite a plethora of studies on MDSCs in mice and men, the precise hematopoietic origin and lineage-association still remain a matter of debate. Broadly accepted is the notion that MDSCs stem from immature myeloid cells (IMCs) and can be subdivided into granulocytic/neutrophilic MDSCs (G-MDSCs) and monocytic MDSCs (M-MDSCs). Current MDSC concepts suggest that differentiation of IMCs into mature granulocytes, macrophages or dendritic cells (DCs) in bone marrow is skewed towards MDSCs in cancers, chronic inflammation, infection, and many other diseases.

Project 1: The emerging role of myeloid-derived suppressor cells in asthma exacerbation

Recently, we showed that adoptively transferred MDSCs were recruited to the lungs of asthmatic mice and reduced lung inflammation. However, there is limited knowledge on the role of MDSCs in lung diseases (Figure 1), and particularly the role of MDSCs in asthma exacerbation, a mixed infection and exaggerated inflammatory condition, remains poorly understood. Influenza A virus (IAV) is a major human pathogen that infects millions of people worldwide every year and causes significant morbidity and mortality particularly in patients suffering from lung diseases like asthma, creating substantial therapeutic challenges. Considering the strong T cell suppressive function of MDSCs, we aim to study the anti-inflammatory potential of MDSCs in a murine house dust mite (HDM) model of IAV-induced asthma exacerbation.

S. Kolahian

Figure 1. The role of myeloid-derived suppressor cells in lung diseases.

Selected publications:

  • Kolahian S, et al. European Respiratory Journal 2016
  • Nowroozilarki N, et al., Kolahian S. Immunology letters 2018

Project 2: Characterizing the emergence of myeloid-derived suppressor cell subsets in pulmonary fibrosis compared to asthma

The immune system has generated a variety of mechanisms to achieve and maintain tolerance both centrally and peripherally. Failure to maintain immune tolerance to a harmless antigen or the exuberant response to a pathogen results in the development of inflammatory diseases or severe fibrotic diseases such as IPF (Figure 2). Regulatory immune cells such as MDSCs, T regulatory cells (Tregs), B regulatory cells (Bregs), and tolerogenic dendritic cells (tDCs) play an indispensable role in maintaining immunological hemostasis. Among those, the role and characterization of MDSCs in IPF has not been clarified. We hypothesize that the strong immunosuppressive and anti-inflammatory activity of MDSCs may inhibit the transition of inflammation to lung fibrosis. Particularly, we would like to compare our data from asthma model with another lung disease model, i.e. pulmonary fibrosis, to be able to understand the different character of MDSCs in models that they start with inflammation and transfer to remodelling and fibrosis.

S. Kolahian

Figure 2. Effect of regulatory immune cells on fibrogenesis.

Selected publications:

  • Kolahian S, et al. American Journal of Respiratory cell and Molecular Biology 2016
  • van Geffen C, et al, Kolahian S. Frontiers in Immunology 2021.

Project 3:  Immuno-pharmacological targets for generation, activation and recruitment of MDSCs in lung diseases

Previously, we showed that adoptive transfer of MDSCs dampens lung inflammation in murine models of asthma through cyclooxygenase-2 and arginase-1 pathways. Here, we further dissected this mechanism by studying the role and therapeutic relevance of the downstream mediator prostaglandin E2 receptor 4 (EP4) in a murine model of asthma. We showed that EP4 agonism alone or Arg1 administration ameliorated lung inflammatory responses and histopathological changes in asthmatic mice. Our results provided evidence that MDSCs dampen airway inflammation in murine asthma through a mechanism involving EP4 (Figure 3). Therefore, we aim to further characterize the role and downstream pathways of EP4 receptor on immunosuppressive MDSCs in asthma and to elucidate the risk-benefit ratio of EP4 receptor agonists as a new generation of bronchodilator/anti-inflammatory medication in asthma therapy. The other pharmacological targets for generation, activation and recruitment of MDSCs are also under investigations.

S. Kolahian

Figure 3. Effect of EP4 agonism on generation, activation and recruitment of MDSCs.

Selected publications:

  • van Geffen C, et al, Kolahian S. Frontiers in Immunology 2021
  • Deißler A, Kolahian S*, Quante M*. Immunology letters 2021 (*contributed equally)
  • Cebulla D, van Geffen C, Kolahian S.  Pharmacology & Therapeutics 2023
  • van Geffen C,et al, Kolahian S. Frontiers in Immunology 2022

Project 4:  Myeloid-derived suppressor cell and dendritic cell (DCs) interaction and impact on T cell response in asthma

Following up on our previous findings on the anti-inflammatory role of MDSCs in asthma models and significant reduction of airway inflammation and remodeling, we hypothesize that the strong immunosuppressive activity of MDSC may impact T cell response through interaction with DCs. To this end, we aim to study the interaction of MDSCs and DCs and their impact on T cell response and different level of MHC molecules expression and antigen presentation in asthma. As both cell types play very important role in asthma, we aim to clarify the unknown interaction of these two cells types with each other in asthma setting. This project is a collaboration with the DC lab in Marburg, led by Dr. Johannes Mayer

S. Kolahian

Figure 4. The interaction of MDSCs and DCs and the impact on T cell response

Project 5:  The emerging character of myeloid-derived suppressor cell isolated from IL-6, IL-10 and IL-17 knockout mice

In this project, we aim to further unravel the mechanisms of MDSC generation and suppressive activity using different knockout mice. In this project we attempt to establish murine bone marrow, spleen, lung and blood-derived cell cultures from IL-6, IL-10 and IL-17 knockout mice, to assess the impact of these specific knockouts on the generation procedure and the suppressive activity as well as genomic/metabolomic character of both PMN- and M-MDSC.

Selected publications:

  • Kolahian S, et al. European Respiratory Journal 2016
  • van Geffen C, et al, Kolahian S. Frontiers in Immunology 2021

Project 6:  Contribution of MDSC subsets on bacterial-induced asthma protection and / or asthma exacerbation

Early life natural microbial exposure has been identified as an important environmental condition that provides asthma protection / exacerbation at a later stage. We hypothesize that a part of the strong allergy protective / harmful effect of microbial exposure may be driven by MDSCs and the two different subsets of MDSC, PMN- and M-MDSCs, may show different suppressive activity in prenatal and postnatal stages of asthma tolerance / exacerbation. We also hypothesize that the signals that drive MDSCs generation and activation in prenatal and postnatal asthma tolerance / exacerbation by microbial exposure may differ from each other and that particularly the character of MDSCs in prenatal and postnatal stages may differ, resulting in different forms of immunomodulation.

 Contact person: PD Dr. Saeed Kolahian, Email: ; Tel. +49 6421 / 28-66048

Group members of AG Kolahian:

  • PD Dr. Saeed Kolahian, Principal Investigator
  • Chiel van Geffen, PhD student
  • Friederike Wulf, MD student
  • Fabian Bleise, MD student
  • Nora Vedder, MD student
  • Philipp Gercke, MD student
  • Nikoleta Lautenschlager, MD student
  • Jakob Schieb, MD student
  • Tim Lange, MD student
  • Tobias Brunn, MD student
  • Charlotte Vetter, MD student
  • Katharina Parzefall, TA